Effect of gamma irradiation of red blood cell units on T-cell inactivation as assessed by limiting dilution analysis: implications for preventing transfusion-associated graft-versus-host disease

Transfusion-associated graft-versus-host disease can be prevented by treating cellular blood products with gamma irradiation. A wide range of gamma irradiation dose levels has been used in routine practice. We used limiting dilution analysis, which measures clonable T cells, to assess the influence of 500 to 3,000 cGy of gamma irradiation delivered from a 137Cs source on T cells when delivered in situ to ADSOL- preserved red blood cell (RBC) units in blood bags. In a series of experiments using RBC units irradiated within 24 hours after collection, 1,500 cGy inactivated > 4 log10 of T cells; however, viable T cells were detected in all experiments. With 2,000 cGy, a > or = 4.7 log10 decrement in T-cell growth occurred in 7 of 8 experiments. With 2,500 or 3,000 cGy, no T-cell growth (> 5 log10 depletion) was detected. Comparable effects were observed with ADSOL-preserved RBC units in the standard PL 146 plastic container and in the recently developed PL 2209 plastic container. T-cell inactivation, as a function of gamma irradiation dose, was similar when either a 137Cs or a linear accelerator source was used. T cells isolated from ADSOL-preserved RBC units after storage for 7 and 21 days, although reduced in number as compared with a fresh unit stored for 24 hours, were viable, capable of proliferation, and susceptible to inactivation by gamma irradiation. Using a sensitive in vitro assay for T-cell proliferation, we found that a gamma irradiation dose of 2,500 cGy may be required to completely inactivate T cells in RBC units.     

Contrast enhancement of magnetic resonance images by chromium EDTA: an experimental study

Chromium EDTA was evaluated as an intravenous contrast agent for magnetic resonance (MR) imaging in vitro and in vivo in rabbits and rats. The effect of Cr EDTA on T1 and T2 values in vitro was first quantitated by spectroscopy at 2.5 MHz, followed by animal trials in which the effects of intravenous injection of Cr EDTA on calculated T1 MR images (obtained by the spin- warp technique at 1.7 MHz) were determined. Following administration of chromium EDTA, differences in T1 values between normal and abnormal kidneys were noted, renal hydronephrosis and renal ischemia were readily identified by the pattern of change in T1, and changes were observed in the normal rabbit brain and in tumors implanted in rats. It is concluded that the use of stable paramagnetic metal ion chelates, such as Cr EDTA, as intravenous contrast agents in MR imaging is feasible and that such agents would make possible the observation of tissue vascularity, breakdown of the blood-brain barrier, and renal function.     

Pulmonary histiocytosis X: evaluation with high-resolution CT

Eighteen patients with pulmonary lesions of histiocytosis X were studied with high-resolution computed tomography (CT). Thin-walled cysts were found in all but one patient. The other abnormalities included nodules (n = 14), cavitated nodules (n = 3), thick-walled cysts (n = 7), reticulation (n = 4), ground-glass opacities (n = 4), and irregular interfaces (n = 4). The lesions were most often diffuse (n = 16), with a topographic predominance in the upper or middle lung zones in nine patients. Comparison of CT scans and chest radiographs shows that small and large cysts and micronodules are better detected with CT. Comparison of abnormalities found in patients in the early and late stages of the disease, as well as the evolution observed in one case, suggests that CT patterns progress from nodules to cavitated nodules and thick-walled cysts to cysts to confluent cysts.     

Focal and diffuse liver disease studied by quantitative microstructural sonography

Quantitative microstructural sonography differs from conventional sonography in several ways. The frequency as well as the amplitude of echoes is recorded and assessed using spectral analysis techniques. The effects of diffraction of the ultrasound beam are calibrated, as are the transfer characteristics of the system. Studies of patients with alcoholic liver disease revealed significantly increased attenuation, heterogeneity of scatterers, and local scattering strength in those with severe disease; in contrast, patients with mild cirrhosis exhibited decreased local scattering strength compared to normal individuals. Using retrospective three-parameter discriminant analysis, 23 out of 24 patients were successfully categorized, suggesting that the parameters used were capable of measuring microstructural changes associated with these disease states. Parameters varied widely among 6 types of hepatic tumors, suggesting that this method may offer promise in distinguishing tumors from normal cases and alcoholic liver disease as well as from each other. Further applications and evaluation of this method appear justified.     

Interstitial Granulomatous Dermatitis with Plaques

An 8‐year‐old male presented with several 1–4 cm, indurated, brownish‐red nodules with superficial, punctate hemorrhagic crusts localized to the groin, which developed over several weeks. An initial biopsy was consistent with Langerhans cell histiocytosis. A work up, including a chest and abdominal CT scan demonstrated a large mediastinal mass which was diagnosed as precursor T cell lymphoblastic lymphoma. Treatment with a chemotherapeutic protocol resulted in shrinkage of both the mediastinal and cutaneous lesions. Late in the course of treatment the cutaneous lesions rapidly recurred and spread to various sites. A second skin biopsy showed an extensive diffuse infiltrate of histiocytic‐appearing cells extending from the papillary dermis into the superficial subcutis. The cells had markedly pleomorphic, vesicular nuclei and abundant amphophilic cytoplasm. Numerous mitotic figures were present. The neoplastic cells were S‐100 protein and CD1a positive by immunohistochemistry. The histopathologic diagnosis was Langerhans cell sarcoma. Gene rearrangement studies demonstrated clonal rearrangement of the T cell receptor gamma gene in specimens from both the mediastinal mass and one of the recurrent cutaneous lesions. The sizes of the PCR products were identical demonstrating a clonal relationship between the two neoplasms.     

Neurofibromatosis of atypical presentation

Neurofibromatosis (NF) is considered to be a heterogeneous neuroectodermal disease clinically defined by the presence of neurofibromas, multiple café-au-lait spots, intertriginous freckles and Lisch nodules. Mosaicism explains atypical presentations of the disease. Early mutations, before tissue differentiation, give rise to generalized disease. We report an atypical presentation of neurofibromatosis with an unusual distribution of neurofibromas, a peculiar, clinically and pathologically, neurofibroma on the trunk and the association with an ovarian serous cystoadenofibroma.     

Mycotic aneurysms in intravenous drug abusers: the utility of intravenous digital subtraction angiography

Two-hundred thirteen intravenous digital subtraction angiographic (DSA) examinations were performed on 195 intravenous drug abusers to rule out the possibility of a mycotic aneurysm in a groin, neck, or upper extremity infection. Twenty-three surgically proved cases of mycotic aneurysm were correctly identified with no false positive results. In addition, six cases of major venous occlusion were documented. We present the results of our experience and conclude that DSA is an effective and cost-efficient method of examining this high risk patient population.     

Potassium channels of the insulin-secreting B cell

Ionic and electrical events play a central role in the stimulus-secretion coupling of the pancreatic B cell. Potassium permeability is critically involved in the regulation of B cell membrane potential and insulin secretion. In the absence of glucose, membrane potential remains stable, around -65 mV. This resting potential is mainly determined by the high potassium conductance of the membrane. The ATP generated by glucose metabolism in B cells blocks the K+(ATP) channels controlling resting membrane potential. Thus, glucose metabolism leads to closure of the ATP-dependent potassium channels; the resulting decrease in K+ permeability induces depolarization and opening of voltage-activated Ca-channels. The subsequent increase in Ca2+ influx raises the cytoplasmic concentration of free Ca2+, which in turn triggers exocytosis of secretory granules. Other types of K+ channels have also been identified in the B cell, such as voltage- and Ca(2+)-dependent K+ channels, which are not a target for the action of glucose, but may play a role in the repolarization of spikes. The modulation of insulin release by some hormones and neurotransmitters involves, among other mechanisms, an interference with the plasma membrane K+ conductance. Thus, galanine, somatostatin and adrenaline, which inhibit insulin release, increase K+ conductance by a G protein-dependent mechanism; both peptides were reported to open ATP-sensitive K+ channels in insulin-secreting cell line RINm5F. It was also observed that extracellular purine nucleotides could interfere with K+ channels. Among the various drugs interfering with insulin secretion, sulfonylureas, such as tolbutamide and glibenclamide, directly inhibit ATP-dependent K+ channels in the B cell membrane and thereby initiate insulin release. In contrast, potassium channel openers such as diazoxide, antagonize the effects of glucose by increasing K+ permeability of the B cell membrane. Furthermore, other classes of drugs have recently been shown to interact with K+ (ATP) channels. Thus, K+ channels of the pancreatic B cell, particularly ATP-dependent ones, play a crucial role in the electrophysiology of insulin secretion; they are an important target for pharmacological agents designed to modulate this secretion.     

Brucellar and tuberculous spondylitis: comparative imaging features

Radiographs, scintigrams, computed tomographic scans, and magnetic resonance (MR) images of 17 patients with brucellar spondylitis and 15 with tuberculous spondylitis were analyzed to identify distinguishing features. Characteristic findings of brucellar spondylitis included predilection for the lower lumbar spine (68% of lesions), bone destruction limited to the end plates, disk collapse (16 of 19 disks), and granulation tissue or localized soft-tissue edema (17 of 19 sites). MR imaging showed diffuse increased signal in vertebrae and disks on long repetition time (TR)/echo time (TE) images in four patients and focal increased signal with normal disks in one. Epidural extension was best seen on short TR/TE images in four. Tuberculous spondylitis was characterized by predilection for the midthoracic spine (73%), vertebral destruction with gibbus deformity (60%), disk collapse, and paraspinal abscesses (14 of 15). On MR images signal intensity of affected vertebrae was similar to but more severe than findings in patients with brucellar spondylitis. Scintigraphy was the least helpful in differentiating the two infections. Lesions of tuberculous spondylitis affecting the lower lumbar spine were difficult to differentiate from those of brucellar spondylitis.